This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly, but treatments are lacking. The goal of this translational research program is to protect and restore vision in AMD using stem cell replacement therapy. Specific Aim 1 is to culture and characterize potentially therapeutic cell types, including forebrain-derived human neural stem cells and human neural stem cells modified to secrete specific neuroprotective factors, including glial derived growth factor. Specific Aim 2 is to transplant these cells to the eyes of rodent models with retinal degenerations to test donor cell survival, evidence of functional and morphological rescue and risk of treatment complications. Specific Aim 3 is to define and optimize the cell delivery procedure and dosage and then evaluate safety and biodistribution in rhesus monkeys. Normal eyes will be studied first, followed by a test of efficacy in our unique rhesus monkey model of age-related macular degeneration. Successful completion of this research will pave the way towards human clinical trials that could have considerable impact on the clinical outcomes for this major blinding condition. In the past year we completed a study showing the feasibility and safety of stem cell transplantation to the monkey retina, and demonstrated that stem cell transplants significantly slowed vision loss and morphological changes in a transgenic mouse model of hereditary retinal degeneration.